Photochemical desulfonylation of N-tosyl amides by 2-phenyl-N,N′- dimethylbenzimidazoline (PDMBI)

Article abstract of DOI:10.1055/s-2005-872693

Photoinduced electron transfer reaction between N-tosyl amides and 2-phenyl-N,N′-dimethylbenzimidazoline (PDMBI) provides an efficient approach for the desulfonylation of N-tosyl amides. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-872693

2510
LETTER
Photochemical Desulfonylation of N-Tosyl Amides by 2-Phenyl-N,N¢-
Dimethylbenzimidazoline (PDMBI)
Photochemical
De
i
sulfony
a
lation of
N
n
-Tosyl Amid
g
es Liu, Zhengang Liu, Yu-Lu Zhou, Wei Zhang, Li Yang, Zhong-Li Liu,* Wei Yu*
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, P. R. of China
Fax +86(931)8625657; E-mail: yuwei@lzu.edu.cn
Received 28 July 2005
imines.11 Since the N–S bond in N-tosyl amides could be
broken by electrochemical reduction,12 it is expected that
N-tosyl amides would be deprotected by photoexcited
PDMBI. Indeed, irradiation (>300 nm) of N-tosyl amides
1 with PDMBI in wet acetonitrile at ambient temperature
afforded the deprotected amides 2 in excellent yields
(Scheme 1, Table 1).
Abstract: Photoinduced electron transfer reaction between N-tosyl
amides and 2-phenyl-N,N¢-dimethylbenzimidazoline (PDMBI) pro-
vides an efficient approach for the desulfonylation of N-tosyl
amides.
Key words: N-tosyl amides, deprotection, photoinduced electron
transfer, 2-phenyl-N,N¢-dimethylbenzimidazoline
The protection of amines or amides by sulfonyl groups is
a common method in organic synthesis.1 The resultant
sulfonamides or N-acyl sulfonamides are stable to a vari-
ety of reaction conditions, such as alkaline hydrolysis and
catalytic reduction. While this stability contributes to the
usefulness of sulfonyl protection, it also limits the scope
of utility, because traditional deprotection methods re-
quire drastic reductive2 or acidic3 conditions, which are
incompatible with incorporated sensitive functional
groups. Therefore, it is much desirable to develop new
deprotection methods, which could remove the sulfonyl
group and recover the amines or amides under mild con-
ditions. Indeed, many new methods for deprotecting sul-
fonamides have recently been reported, including the use
of SmI2,4 Mg in methanol,5 TBAF,6 iodotrimethylsilane7
or Bu3SnH.8 Deprotection of sulfonamides could also be
achieved by photochemical approaches, including direct
UV photolysis at 254 nm9a,b and photosensitized reac-
tions.9c,d The latter approach, with b-naphthoxide or elec-
tron-rich arenes as sensitizers and sodium borohydride as
co-reductant, is more advantageous, because longer wave-
length could be used and side reactions arising from short
wavelength light absorption could be avoided. Herein we
wish to report an efficient new method for desulfonylation
of N-tosyl amides by photoinduced electron transfer
reaction with 2-phenyl-N,N¢-dimethylbenzimidazoline
(PDMBI) which acts as the electron and hydrogen donor.
Me
Ts
H
PDMBI,
N
H
R2
N
R2
N
R1
MeCN–H2O (13:1)
R1
N
Ph
O
hν, λ > 300 nm
O
Me
2
1
PDMBI
Scheme 1
In a typical experiment, a mixture of N-tosyl amide (1, 1
mmol) and PDMBI (1.2 mmol) in 7 mL of acetonitrile
containing 0.1 mL of water was irradiated with a Pyrex-
filtered (>300 nm) high-pressure mercury lamp under ar-
gon atmosphere at ambient temperature. After completion
of the reaction as monitored by TLC, the solvent was re-
moved under reduced pressure and the deprotected amide
2 was isolated from the residual by flash chromatography
1
over silica gel and identified by comparing its H NMR
and EI-MS spectral data with those reported in the litera-
ture. Beside 2, another highly polar product was also ob-
tained, which was characterized to be PDMBI+SO2Ar–.
The results are listed in Table 1.
It is seen from Table 1 that this reaction worked well with
a variety of N-tosyl amides. Excellent yield was obtained
even with the bulky substrate 1c. In the case of cinnamoyl
sulfonamide (1g), deprotection was achieved with the
conjugated double bond intact. Attempt was also made to
desulfonylate tert-butoxy substituted substrate 1d. How-
ever, the reaction did not proceed. The electron donating
effect of the tert-butoxy group possibly renders the com-
pound inert to accept an electron from excited PDMBI.
Regarded as an NADH model compound, PDMBI has
been well studied as a biomimetic reducing agent from
mechanistic and synthetic points of view.10 Hasegawa and
coworkers have used PDMBI as an electron and hydrogen
donor to achieve photoinduced synthetically useful trans-
formations,10h–k such as Ca–O cleavage of a,b-epoxy ke-
tones for preparation of b-hydroxy ketones.10h,i We also
found that photoexcited PDMBI could reduce aromatic
On the other hand, it was interesting to note that N-tosyl
amines turned out to be unreactive to this reaction condi-
tion. Therefore, this approach could be used to achieve the
chemoselective deprotection of N-tosyl amido group in
case that both amino and amido groups are protected by
tosyl group. Indeed, irradiation of N-tosyl-N-[2-(tosyl-
amino)ethyl] acetamide (3) for 12 hours gave the
SYNLETT 2005, No. 16, pp 2510–2512
0
4
.1
0
.2
0
0
5
Advanced online publication: 21.09.2005
DOI: 10.1055/s-2005-872693; Art ID: U25205ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Photochemical Desulfonylation of N-Tosyl Amides
2511
Table 1 Photoinduced Deprotection of N-Tosyl Amides 1 by PDMBIa
Entry
Substrate
Time (h)
Product
Yield (%)b
R1
R2
1
2
1a
1b
1c
1d
1e
1f
PhCH2
PhCH2
PhCH2
PhCH2
PhCH2
PhCH2
PhCH2
n-Bu
Me
10
12
14
20
10
8
2a
2b
2c
2d
2e
2f
90
96
94
NR
98
97
98
82
90
90
n-Bu
t-Bu
t-BuO
PhCH2
Ph
3
4
5
6
7
1g
1h
1i
PhCH=CH
Me
8
2g
2h
2i
8
20
14
10
9
Cyclohexyl
Ph
Me
10
1j
Me
2j
a For reaction conditions, see text.
b Isolated yields. All products are known compounds and were characterized by EI-MS, 1H NMR and 13C NMR spectroscopy.13
hν
monodeprotected 4 in 91% yield (Scheme 2). The
PDMBI*
PDMBI
PDMBI
1
PDMBI
PDMBI
chemoselectivity of this desulfonylation method for acyl
sulfonamides should allow its further application in or-
ganic synthesis.
ET
ET
– H+
PDMBI+
1
Ts
1.2 equiv PDMBI
MeCN–H2O (14:1)
H
_
Ts
N
N
Me
Ts
Me
SO2Ar
R2
N
N
H
H
hν, λ > 300 nm
O
PDMBI+SO2Ar–
O
N
R1
PDMBI
91%
3
4
O
Scheme 2
PDMBI
2
In the dark control experiment, the same reaction mixture
of N-tosyl amide 1 and PDMBI was refluxed for four
hours, but no reaction took place. The reaction also did not
take place in the absence of PDMBI under the same irra-
diation condition. In view of the general PDMBI photore-
ductive mechanism,10c–f,h this reaction can be rationalized
as a photoinduced electron transfer reaction as shown in
Scheme 3. In the scheme the reaction is initiated by single
electron transfer from excited PDMBI to N-tosyl amide 1
that produces the radical cation of PDMBI and the radical
anion of 1. It is well known that formation of radical ions
would remarkably weaken the chemical bond in the
species, hence facilitate bond breaking.14 Maslak and co-
workers have termed unimolecular fragmentation of
radical ions as mesolytic cleavage and demonstrated the
tremendous facilitation of bond cleavages obtainable
from the mesolytic process.15 In the present case the
mesolytic cleavage of PDMBI radical cation (catio-
mesolysis) leads to deprotonation from PDMBI giving the
PDMBI radical, and the mesolytic cleavage of the radical
Scheme 3
anion of 1 (aniomesolysis) remarkably weakens the N–S
bond in 1, hence facilitates the desufonylation. The amide
radical thus formed abstracts a hydrogen from PDMBI,
producing the product 2. The PDMBI radical might also
subject to electron transfer with 1 to propagate the chain
process, as indicated by the formation of PDMBI+SO2Ar–
during the reaction (Scheme 3).
In summary, N-tosyl amides can be easily deprotected by
photoinduced electron transfer reaction with DMPBI in
the presence of N-tosyl amino functionality. This provides
a simple, mild and chemoselective desulfonylation
method.
Acknowledgment
We thank the National Natural Science Foundation of China (grant
No. 20372030) for financial support.
Synlett 2005, No. 16, 2510–2512 © Thieme Stuttgart · New York

2512
Q. Liu et al.
LETTER
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Synlett 2005, No. 16, 2510–2512 © Thieme Stuttgart · New York